For the second time in four months, the FDA has issued a warning letter to a supplier of active pharmaceutical ingredients for failing to follow regulatory manufacturing standards. The move comes as the agency attempts to step up oversight of the pharmaceutical supply chain, notably in China, where the company first attracted FDA attention.

The latest missive sent to Novacyl concerns a facility in Thailand, where FDA inspectors last April found several problems. These included a lack of controls to prevent unauthorized manipulation of raw electronic data in a lab; a failure to retain complete raw data during testing, and the quality unit failed to provide proper oversight of cleaning operations and contamination problems.

There were also problems with testing. The agency cited Novacyl for “significantly lower quality material” used in a study to validate products and noted that one of its employees “selectively” invalidated data during related substance testing. These were among several issues that the FDA cited as “serious” deviations from good manufacturing practices.

A spokeswoman for Novacap, which is the parent company and is based in France, sent us a note saying Novacyl “diligently answered” and “implemented actions” stipulated by the FDA since the inspection last year. But she acknowledged the February 27 warning letter “requires additional stronger actions to be taken” at the site in Bangpoo, Thailand, which makes aspirin, according to the Novacap website.

The FDA has Novacyl under a microscope. Last December, the agency sent a separate warning letter after an inspection at facility in Wuxi, China, found various infractions. For instance, employees made changes to an impurities test without documentation or justification and, instead, relied on handwritten notes on a chromatogram that was discovered in a drawer.

In both warning letters, the FDA tells Novacyl to develop a comprehensive plan to correct the problems. “We are confident in our capacity to implement a suitable action plan in due time without discontinuing our current sales activities,” the Novacap spokeswoman writes us. The facility makes aspirin ingredients, according to the Novacap web site.

As we have noted previously, pharmaceutical production in Asia, particularly China, is of increasing concern as companies there make a growing number of products or ingredients that find their way into the U.S. supply chain. The FDA opened an office in China in 2008 after a recall of the heparin blood thinner, which was made with a fake Chinese active ingredient and was linked to 246 deaths in the U.S.

The FDA wants to station more inspectors in China but has been stymied for more than a year, because the Chinese government has not issued enough visas. Since November, however, the agency signed two agreements with China that were linked to an agreement reached in late 2013 to expand FDA activities there. The FDA plans to add more inspectors shortly. We asked the agency for an update and will pass along any reply.

Good morning, everyone, and welcome to another working week. We hope the weekend respite was relaxing and you had time to hit the proverbial refresh button, because that familiar routine of meetings and deadlines and what-not has just returned. You knew this would happen, though, yes? So time to get started. And, of course, please join us as we quaffe another cup of stimulation in preparation. We hope your day is smashing and, as always, do keep in touch. We enjoy hearing interesting tales…

Merck signed a five-year deal with NGM Biopharmaceuticals to research and develop biologics for treating diabetes and obesity, in its latest bid to introduce new products, The Wall Street Journal says. Merck will provide a $94 million upfront payment and a $106 million equity investment for a 15% stake, and also fund $250 million of NGM R&D projects over the next five years, although NGM has full authority to control R&D. Merck R&D chief Roger Perlmutter and NGM chief scientific officer, Jin-Long Chen, by the way, once worked together at Amgen.

Valeant Pharmaceuticals agreed to pay about $10 billion to buy Salix Pharmaceuticals, in a deal that will take Valeant into a growing, multibillion-dollar market for drugs treating stomach disorders, The Wall Street Journal reports. The move doubles Valeant debt. And Salix is a tarnished asset. In November, Salix disclosed a revision to its wholesale-inventory levels that suggested demand for its drugs might not be as high as previously thought. In recent months, the company’s chief financial officer and chief executive have left.

Johnson & Johnson, which paid more than $2 billion to resolve a criminal probe over its antipsychotic drug Risperdal, knew the medicine caused boys to develop female breasts and failed to alert regulators, doctors and patients, a lawyer argued during close statements late last week, Bloomberg News reports. The health care giant is being sued by the parents of an autistic man who developed size 46 DD breasts while on the medicine. The case is the first in which a jury will decide whether J&J and its Janssen unit are liable for mishandling the medicine.

Bristol-Myers Squibb has announced two deals valued at $1.6 billion to bolster its oncology pipeline, Bloomberg News informs us. One deal involves paying up to $1.25 million for Flexus Biosciences, a privately held drug developer; this $800 million in an upfront payment and up to $450 million of milestone payments. The other deal is a research agreement valued at $339 million, plus royalties, with Rigel Pharmaceuticals.

Novo Nordisk says it received positive results from a Phase II trial of an oral version of a long-acting GLP-1 drug for treating type 2 diabetes, opening the door to another, final phase of trials before potential regulatory approvals, writes Reuters.

Johnson & Johnson is in talks to sell its Cordis unit, with Cardinal Health for as much as $2 billion, although no agreement has been reached and the talks could still fall apart, Bloomberg News says.

The China Food and Drug Administration is proposing to amend its good clinical practices to add more specific responsibilities for sponsors, ethics committees and sites as part of efforts to further protect study subjects, Outsourcing Pharma writes.

A federal judge ruled that Walgreens did not violate the law when firing a pharmacist who had moral objections to administering flu vaccines, The Legal Intelligencer reports.

A bankruptcy judge late last week approved the sale of Dendreon assets to Valeant Pharmaceuticals for $495 million, after a last-minute modification to the bid, The Wall Street Journal writes.

Pfizer says the FDA has accepted for priority review a supplemental drug application of its Rapamune immunosuppressant for lymphangioleiomyomatosis, a rare, often-fatal lung disease, Pharma Times says.

With an aim to boost the active pharmaceutical ingredients manufacturing industry on a bigger scale in India, the central government has decided to declare the year 2015 as ‘Year of API,’ PharmaBiz tells us.

Japanese biopharmaceutical company Sosei Group has acquired Heptares Therapeutics, in a deal that could be worth up to $400 million, Pharmaceutical Business Review writes.

Ferring has signed a deal with South Korean group CTCBIO to acquire rights to its novel oral drug delivery technology for an undisclosed amount, according to Pharma Times.

Good morning, everyone, and how are you today? A shiny sun is hovering over the frigid Pharmalot campus, where the officials mascots and the shortest of short people are all snoozing comfortably. As for us, we are as busy as ever, foraging for interesting items and gazing meaningfully at our ever-growing to-do list. No doubt, you may relate. So time to hoist the mandatory cup of stimulation and get cracking. Hope you have a swell day and accomplish much. And do drop us a line if you run across anything fascinating…

Regeneron Pharmaceuticals ' Eylea bested Roche’s Lucentis and Avastin in a study sponsored by the U.S. National Institute of Health in diabetes-related vision loss, although the results showed the effect was strongest in patients who had poorer vision before starting treatment, CNBC says. The results are likely to encourage use of Avastin, which costs $50 a dose for eye indications, compared with $1,950 for Eylea and $1,200 for Lucentis, even though the medication is not approved to treat diabetic macular edema, unlike the other two drugs.

A new analysis claims that the threshold used by the U.K.’s National Institute for Health and Care Excellence when gauging the cost-effectiveness of new drugs is too high, which means the U.K.’s National Health Service is paying too much for new medicines, writes Pharma Times. The analysis notes that currently NICE uses a threshold of £30,000, or $46,000, per Quality Adjusted Life Year (QALY) but claims this should be £13,000, or $20,000, to provide most benefit across the NHS.

In a bid to reduce its dependency on China for bulk drugs, the Indian government plans to come up with strategies to increase the bulk drug capacity within a stipulated time frame of two months, Business Insider says. One part of the plan is to revive Hindustan Antibiotics, a state-run operation that was established in 1954 by the government, the World Health Organization and Unicef, but later ran into financial difficulties and has been struggling ever since.

The White House named Silicon Valley veteran DJ Patil to the position of chief data scientist and deputy chief technology officer for data policy, a new position that underscores the mainstream importance of big datawith a strong focus on healthcare, MedCity News writes.

Actavis ceo Brent Saunders says the drug maker has sidelined large deals that involve moving into new therapeutic areas as it focuses on cutting its debt, but that the drugmaker continues to look at small acquisitions that fit with its current businesses, Reuters reports.

The FDA granted priority review for a Roche drug called cobimetinib in combination with its Zelboraf medication to treat a serious form of skin cancer known as BRAF V600 mutation-positive melanoma, The Wall Street Journal tells us.

Good morning, everyone, and welcome to the working week. We hope the weekend respite was refreshing and invigorating because the usual routine of meetings, deadline and what-not has returned with its customary vengeance. To cope, yes, we are brewing more cups of stimulation and, as always, invite you to join us. A little stimulation can be a good thing, yes? And no prescription is required. Meanwhile, here are some tidbits to get you started. We hope you have a splendid day and do stay in touch…

AbbVie has agreed to provide its Viekira Pak hepaitis C treatment to the ADAP Crisis Task Force, which provides HIV drugs to U.S. states, at a substantial discount, Bloomberg News reports. The organization for 50-plus state programs and served about 150,000 patients in June 2013. The task force does not have a similar deal with Gilead Sciences, which refused to negotiate, Britten Pund, associate director of health-care access for the National Alliance of State & Territorial AIDS Directors, tells the news service.

Merck is funding the testing of lower dosages of its controversial Zilmax drug for cattle growth in a move that livestock experts say is crucial if the company is to resume sales of the product to the U.S. beef industry,Reuters writes. Nearly 18 months after Merck pulled the drug from the U.S. and Canadian markets after videos and photographs showed Zilmax-fed cattle turning up in a distressed state, either lame or with hooves missing at slaughterhouses, scientists at Texas Tech University are testing beef carcasses taken from cattle fed different concentrations of Zilmax.

Novartis is closing its manufacturing plant in Puerto Rico as part of a major overhaul and shifting some work to a facility in Lincoln, Nebraska, reports The Lincoln Journal-Star. The shutdown of its Humacao plant will conclude in early 2019 and some 270 employees will be laid off. The Lincoln plant currently makes solid dose and powder forms of Excedrin and Theraflu, but used to make several over-the-counter drugs before Novartis pared down manufacturing operations in 2013 because of quality-control operations that led to a total shutdown in December 2011.

Drug makers may be flocking to Massachusetts from around the U.S. and Europe to open research centers, but for some, California remains a better place to spark entrepreneurial activity, The Boston Globe writes. Some out-of-state companies believe they can easily forge long-distance partnerships with Massachusetts drug makers.“We’re not going to stick an R&D center in Boston,” says James Sabry, senior vice president for partnering at Genentech. “We do deals with Boston companies. But we go wherever the science is.”

The family of a former Catholic priest is suing Novartis after he allegedly suffered brain injury from participating in a clinical trial assessing Jakavi to treat a rare blood disorder, The Daily Mail says. But two months into the trial, which began in 2012 and involved patients with myelofibrosis, Adrian Hailer, 77, began suffering from confusion and memory loss and, by the end of the year, brain damage due to progressive multifocal leukoencephalopathy, or PML, a serious brain infection. Novartis says there is no proven link between its drug and his injuries.

The FDA’s Center for Drug Evaluation and Research says its Office of Generic Drug has hired 923 new employees as of October 2014 in an attempt to increase its staff members to meet review goals set by the Generic Drug Use Fee Act, Regulatory Focus writes.

Colorado legislators are once again being asked to let pharmacists substitute biosimilars for brand-name biologics if a doctor is notified of the change, The Denver Business Journal tells us. The proposal revives an idea that failed in the Legislature two years ago.

Taiwan will allow 13 prescription drugs, including allergy relief nasal sprays and antihistamines, to be sold as over-the-counter medications starting in June, according to BioSpectrum.

Novartis says the European Commission has approved its Cosentyx drug as a first-line systemic treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy, Pharma Times says.

India’s CMO Piramal has acquired Coldstream Laboratories, a sterile injectable contract development and manufacturing organization, based in the U.S. for $30.6 million, Outsourcing Pharma reports.

Following Wockhardt’s decision to end supplies of active pharmaceutical ingredients to the EU market, the UK drug regulator MHRA has updated its statement of noncompliance to include all APIs made by the Indian manufacturer, InPharma Technologist tells us.

Strides Arcolab reached a licensing deal with Gilead Sciences to make and distribute the Tenofovir HIV treatment in developing countries, according to The Economic Times.

Pfizer is eliminating 50 jobs from its Pearl River, N.Y., facility by April, according to the Lower Hudson Valley News, which cited a filing with the New York Department of Labor.

The US is going to make a big pitch for starting negotiations with India on the delayed Bilaterial Investment Promotion and Protection Agreement as officials from both sides meet on January 26, The Business Standard writes.

The town of Jupiter, Fla., filed a lawsuit against CHS Pharma after guaranteeing a $275,000 loan to the drug maker as part of a $3 million investment fund for biotech companies about a decade ago, writes The South Florida Business Journal.

Three pharmaceutical companies in north China’s Hebei Province are under police investigation after media accused them of pollution offenses, local authorities told EastDay.

As if to illustrate why the FDA wants more inspectors in China, the agency recently issued a warning letter to a supplier of active pharmaceutical ingredients based in the industrial city of Wuxi that committed several fundamental manufacturing violations.

Notably, during an inspection last October, FDA inspectors found that employees at the Novacyl Wuxi Pharmaceutical facility failed to keep supporting raw data to verify that products met specifications. In its December 19, 2014, warning letter, the agency described this as a “basic responsibility.”

As an example, the inspectors found that changes were made to an impurities test without documentation or justification. Instead, employees relied on handwritten notes on a chromatogram that was “discovered in a drawer.” Moreover, there was no audit trail to trace who made the changes or when.

We asked Novacap, the parent company which is based in France, for comment and will update you accordingly. The FDA letter, by the way, does not mention which products or ingredients are made at the facility, although the Novacyl website indicates that acetaminophen is manufactured there.

There were other issues that led the FDA to question the quality of products made there. Novacyl failed to properly document or investigate discrepancies, establish appropriate lab controls or record good manufacturing practices which, the FDA noted, raised the likelihood that erroneous data would be recorded.

The agency cited one episode in which an analytical worksheet contained drug sample information but raw data was not properly linked to sample preparations. However, the company explained to the FDA that an analyst remembered the order in which the samples were prepared and placed into a test tube rack. This concerned the FDA.

“We are concerned that you rely on the memory of your employees,” the agency wrote, “rather than on actual supporting documentation. A basic principle of [good manufacturing practices] is to record activities at the time of performance to ensure that complicated activities and critical steps are performed according to written procedures.”

[UPDATE: A Novacap spokeswoman sent us a statement saying that "Novacyl is fully mobilized to diligently address the FDA requests in the coming weeks with the support of a dedicated team of internal and external recognized good manufacturing practice experts. We are confident in our capacity to implement a suitable action plan in due time without any impact on normal business activities."]

Pharmaceutical production in China is of increasing concern as companies there make a growing number of products or ingredients that find their way into the U.S. supply chain. The FDA opened an office in China in 2008 after a recall of the heparin blood thinner, which was made with a fake Chinese active ingredient and was linked to 246 deaths in the U.S.

The FDA wants to station more inspectors in China but has been stymied for more than a year, because the Chinese government has not issued enough visas. Since November, however, the agency signed two agreements with China(here is one and here is the other) that were linked to an agreement reached in late 2013 to expand FDA activities there.

“The December 2013 agreement did not link the issuance of visas with the completion of these documents,” an FDA spokeswoman writes us. “Operationally, however, the Chinese government in early 2014 linked these two commitments. With both documents now signed, we anticipate that the Chinese government will issue the relevant visas in the coming weeks.”

The agency would like to increase the number of U.S. inspectors to 26 from eight. Ten of the new hires would be assigned to inspect pharmaceutical plants, while seven would be assigned to inspect food producers. The last hire would be a managerial person.